| 1. |
- Rejler, Martin, et al.
(författare)
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Framework for assessing quality of care for inflammatory bowel disease in Sweden
- 2012
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group. - 1007-9327 .- 2219-2840. ; 18:10, s. 1085-1092
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To create and apply a framework for quality assessment and improvement in care for inflammatory bowel disease (IBD) patients.METHODS: A framework for quality assessment and improvement was created for IBD based on two generally acknowledged quality models. The model of Donabedian (Df) offers a logistical and productive perspective and the Clinical Value Compass (CVC) model adds a management and service perspective. The framework creates a pedagogical tool to understand the balance between the dimensions of clinical care (CVC) and the components of clinical outcome (Df). The merged models create a framework of the care process dimensions as a whole, reflecting important parts of the IBD care delivery system in a local setting. Clinical and organizational quality measures were adopted from clinical experience and the literature and were integrated into the framework. Data were collected at the yearly check-up for 481 IBD patients during 2008. The application of the quality assessment framework was tested and evaluated in a local clinical IBD care setting in Jonkoping County, Sweden.RESULTS: The main outcome was the presentation of how locally-selected clinical quality measures, integrated into two complementary models to develop a framework, could be instrumental in assessing the quality of care delivered to patients with IBD. The selected quality measures of the framework noted less anemia in the population than previously reported, provided information about hospitalization rates and the few surgical procedures reported, and noted good access to the clinic.CONCLUSION: The applied local quality framework was feasible and useful for assessing the quality of care delivered to IBD patients in a local setting.
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| 2. |
- Rejler, Martin, et al.
(författare)
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Low prevalence of anemia in inflammatory bowel disease: A population-based study in Sweden
- 2012
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 47:8-9, s. 937-942
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Anemia is a well-known complication of inflammatory bowel disease (IBD) with a reported prevalence of 8.8-73.7%. However, knowledge is sparse about the anemia prevalence in a population-based cohort of patients affected by IBD. Materials and methods. The aim of this retrospective, descriptive, population-based study was to determine and analyze the prevalence of anemia for ambulatory (n = 485) as well as for hospitalized patients diagnosed with IBD in 2008 in the Highland Health Care District, Jonkopings County, Sweden. Results. The prevalence of anemia at the annual follow-up in the studied IBD population was 6%, 5% for patients with ulcerative colitis (UC), and 9% for those with Crohns disease (CD). There was a higher rate of anemia at the yearly check up in patients requiring inpatient care during the year. IBD patients, prescribed anti-TNF-alpha treatment, had a higher rate of anemia. Of the hospitalized UC and CD patients (n = 31), 35% and 50%, respectively, had anemia at admission and 6% and 4% had severe anemia (Hb andlt;100 g/L), respectively. Conclusions. The prevalence of anemia in this population was lower than reported previously, probably due to inclusion of all IBD patients in the area in combination with a proactive follow-up model. The prevalence of anemia in this IBD population was similar to the prevalence in the general population. This may indicate that efforts by health care professionals to prevent, identify, and treat anemia in the IBD population have been successful.
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| 3. |
- Spångeus, Anna, et al.
(författare)
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Toe brachial index in middle aged patients with diabetes mellitus type 2 : Not just a peripheral issue
- 2013
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 100:2, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- AimTo explore risk factors for peripheral arterial disease (PAD) as well as the association between toe blood pressure and subclinical and clinical central vascular disease in patients with type 2 diabetes.MethodToe brachial index (TBI) was cross-sectionally analyzed in 742 middle-aged (54–66 years) patients with type 2 diabetes as well as non-diabetic controls and related to other vascular measures (e.g. carotid intima media thickness (IMT), presence of carotid plaque, central arterial stiffness and left ventricular mass index) and previous cardiovascular events.ResultsA TBI ≤ 0.7 was seen in 22% of the patients but only one patient had severe TBI reduction (TBI ≤ 0.3). The corresponding figures in the controls were 13% and 0%, respectively. Mean TBI was significantly lower in patients with type 2 diabetes than in controls (0.81 ± 0.14 vs. 0.87 ± 0.15, p < 0.001). In patients with diabetes, a lower TBI was associated with increased central arterial stiffness (p < 0.001), IMT (p < 0.001) and carotid plaque (p < 0.001) as well as with decreasing glomerular filtration rate (p < 0.001). Lower TBI was found in patients with previous macrovascular ischemic events. Furthermore, TBI was negatively correlated with age (p < 0.001), diabetes duration (p < 0.001) and HbA1c (p = 0.01).ConclusionPAD, assessed with TBI, is common in a Swedish middle-aged diabetes type 2 cohort, affecting about one-fifth. As ankle pressure may be confounded by falsely high values in patients with diabetes due to media calcification we conclude that information about TBI may improve the risk evaluation regarding arteriosclerotic disease in both small and large vessels in type 2 diabetes.
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| 4. |
- Tjomsland, Vegard, et al.
(författare)
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IL-1α Expression in Pancreatic Ductal Adenocarcinoma Affects the Tumor Cell Migration and Is Regulated by the p38MAPK Signaling Pathway
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- The interplay between the tumor cells and the surrounding stroma creates inflammation, which promotes tumor growth and spread. The inflammation is a hallmark for pancreatic adenocarcinoma (PDAC) and is to high extent driven by IL-1α. IL-1α is expressed and secreted by the tumor cells and exerting its effect on the stroma, i.e. cancer associated fibroblasts (CAF), which in turn produce massive amount of inflammatory and immune regulatory factors. IL-1 induces activation of transcription factors such as nuclear factor-κβ (NF-κβ), but also activator protein 1 (AP-1) via the small G-protein Ras. Dysregulation of Ras pathways are common in cancer as this oncogene is the most frequently mutated in many cancers. In contrast, the signaling events leading up to the expression of IL-1α by tumor cells are not well elucidated. Our aim was to examine the signaling cascade involved in the induction of IL-1α expression in PDAC. We found p38MAPK, activated by the K-Ras signaling pathway, to be involved in the expression of IL-1α by PDAC as blocking this pathway decreased both the gene and protein expression of IL-1α. Blockage of the P38MAPK signaling in PDAC also dampened the ability of the tumor cell to induce inflammation in CAFs. In addition, the IL-1α autocrine signaling regulated the migratory capacity of PDAC cells. Taken together, the blockage of signaling pathways leading to IL-1α expression and/or neutralization of IL-1α in the PDAC microenvironment should be taken into consideration as possible treatment or complement to existing treatment of this cancer.
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| 5. |
- Tjomsland, Vegard, et al.
(författare)
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IL-1α Sustains the Inflammation in Human Pancreatic Cancer Microenvironment by Targeting Cancer Associated Fibroblasts
- 2010
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. Our aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effect cross talk between primary PDAC and CAF cell lines propagated from tumors had on the creation and sustenance of an inflammatory environment and what factors that were involved in establishing the inflammation. The coculture of PDAC and CAF cell lines, propagated from tumor tissues, enhanced the levels of inflammatory factors including IL-1α, IL-6, CXCL8, VEGFA, CCL20, and COX-2. The production of these factors correlated with the expression detected in vivo in PDAC tissues. The key producers of nearly all inflammatory factors were the CAFs and not the tumor cells. IL-1α was produced by the tumor cell lines, whereas almost all IL-1RI was expressed by CAFs thus corresponding to their in vivo expression profile in PDAC tissues, indicating a role for the IL-1 signaling cascade in a tumor favorable microenvironment. Neutralization of the IL-1α pathway efficiently diminished the cross talk induced production of inflammatory factors, both in stroma and tumor cells. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one contributing factor in the formation of the inflammatory tumor environment and we propose that the neutralization of IL-1α pathway might be a potential therapy for this cancer.
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| 6. |
- Tjomsland, Vegard, 1978-, et al.
(författare)
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Interleukin 1α sustains the expression of inflammatory factors in human pancreatic cancer microenvironment by targeting cancer-associated fibroblasts
- 2011
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Ingår i: Neoplasia. - : Neoplasia Press. - 1522-8002 .- 1476-5586. ; 13:8, s. 664-675
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Tidskriftsartikel (refereegranskat)abstract
- The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. The aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effects of the cross-talk between primary PDAC and CAF cell lines on the creation and sustenance of the inflammatory tumor microenvironment in pancreatic cancer. The coculture of primary PDAC and CAF cell lines enhanced the levels of inflammatory factors including IL-1á, IL-6, CXCL8, VEGFA, CCL20, and COX-2. CAFs were superior to tumor cells regarding the production of most inflammatory factors and tumor cell associated IL-1á was established as the initiator of the enhanced production of inflammatory factors through the binding of IL-1á to the active IL-1 receptor (IL-1R1) expressed predominantly by CAFs. Furthermore, we found a positive correlation between IL-1á and CXCL8 expression levels in PDAC tissues and correlation between IL-1á expression and the clinical outcome of the patients. This confirmed an important role for the IL-1 signaling cascade in the creation and sustenance of a tumor favorable microenvironment. Neutralization of the IL-1á signaling efficiently diminished the cross-talk induced production of inflammatory factors. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one essential factor in the formation of the inflammatory tumor environment and we propose that neutralization of the IL-1á signaling might be a potential therapy for this cancer.
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| 7. |
- Tjomsland, Vegard, et al.
(författare)
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Pancreatic cancer microenvironment has a high degree of inflammation and infiltrating immune cells in its stroma
- 2010
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, and other cellular components, which work together and create an inflammatory environment favoring tumor progression. The present study aimed to characterize the expression and location of immune cells and investigate inflammatory factors that influence pancreatic ductal adenocarcinoma (PDAC). Methods: qPCRs and immunohistological stainings were performed for inflammatory factors and immune cells localized in tumor tissues from patients with PDAC (N=30). Results: All PDAC tissues had significant increased levels of inflammatory and chemotactic factors such as IL-1α, COX-2, CXCL8, CCL2, and CCL20 as compared to controls. The PDAC stroma, i.e. the fibrosis surrounding the tumor, was the main producer of these factors with the exception of IL-1α, which was expressed by tumor cells and some infiltrating immune cells. The gene expression for immune cell specific markers CD163, CD1c, CD303, and CD8, corresponding to macrophages, myeloid dendritic cells (DCs), plasmacytoid DCs, and cytotoxic T lymphocytes (CTL), respectively, were all significantly increased in PDAC tissues. Immunostaining of the tumor tissue confirmed the elevated levels of infiltrating macrophages, DCs, mature DCs, and cytotoxic T lymphocytes (CTL). The different immune cells were in nearly all cases localized in the fibrotic tissue adjacent to tumor nests. Production of CXCL8 mRNA and protein by the stroma was dependent on the tumor expression of IL-1α. Of importance, we found a correlation in expression of the proinflammatory factor IL-1α and the PDAC patients’ survival time. Conclusion: PDAC cells seem to take advantage of IL-1α to create an inflammatory microenvironment with high degree of fibrosis and the ability to both recruit and activate immune cells and the level of inflammation in this environment influenced the clinical outcome for the patients. Therapies targeting the inflammation might be beneficial for the survival of patients with PDAC.
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| 8. |
- Tjomsland, Vegard, et al.
(författare)
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Semi Mature Blood Dendritic Cells Exist in Patients with Ductal Pancreatic Adenocarcinoma Owing to Inflammatory Factors Released from the Tumor
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Much evidence exists regarding the fact that blood DCs, both myeloid DCs (MDCs) and plasmacytoid DCs (PDCs), are negatively affected in different types of cancer, with both reduced numbers and impaired functionality. Functional impairment of DCs in patients with pancreatic ductal adenocarcinoma (PDAC), may contribute to the poor clinical outcome. The aim of this study was to examine the effects PDAC had on blood DCs and elucidate the underlying mechanism responsible for the DC impairment. Methodology/Principal Findings: We examined the systemic influence PDAC exerted on blood DCs by ex vivo measuring numerous activation and maturation markers expressed on these cells. Furthermore, the effect patient plasma and the inflammatory factors CXCL8 and PGE(2) had on purified MDCs and PDCs from healthy donors was assessed and compared to the DCs existing in PDAC patients. We found a partial maturation of the blood MDCs and PDCs in PDAC patients with significantly enhanced expression of CD83, CD40, B7H3, PDL-1, CCR6, and CCR7 and decreased expression of ICOSL, and DCIR. These changes lead to impairment in their immunostimulatory function. Furthermore, chronic pancreatitis gave rise to DCs with similar semi-mature phenotype as seen in PDAC. Low expression of ICOSL was associated with poor prognosis. We found that the mechanism underlying this semi-maturation of DCs was inflammatory factors existing in the PDAC patients plasma. Of note, PGE2, which is elevated PDAC patient plasma, was one contributing factor to the changes seen in MDCs and PDCs phenotype. Conclusion/Significance: Our findings point to a role for the systemic inflammation in transforming blood MDCs and PDCs into semi-mature cells in PDAC patients and we show a correlation between maturation status and clinical outcome. Thus, means to preserve a functional blood DC compartment in PDAC patients by diminishing the inflammation could facilitate their ability to control the disease and improve survival.
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| 9. |
- Tjomsland, Vegard, et al.
(författare)
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The Desmoplastic Stroma Plays an Essential Role in the Accumulation and Modulation of Infiltrated Immune Cells in Pancreatic Adenocarcinoma
- 2011
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Ingår i: Clinical & Developmental Immunology. - : Hindawi Publishing Corporation. - 1740-2522 .- 1740-2530. ; 2011:212810
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Tidskriftsartikel (refereegranskat)abstract
- Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, which all work together and create an inflammatory environment favoring tumor progression. The present study aimed to investigate the role of the desmoplastic stroma in pancreatic ductal adenocarcinoma (PDAC) regarding expression of inflammatory factors and infiltration of immune cells and their impact on the clinical outcome. The PDAC tissues examined expressed significantly increased levels of immunomodulatory and chemotactic factors (IL-6, TGF beta, IDO, COX-2, CCL2, and CCL20) and immune cell-specific markers corresponding to macrophages, myeloid, and plasmacytoid dendritic cells (DCs) as compared to controls. Furthermore, short-time survivors had the lowest levels of DC markers. Immunostainings indicated that the different immune cells and inflammatory factors are mainly localized to the desmoplastic stroma. Therapies modulating the inflammatory tumor microenvironment to promote the attraction of DCs and differentiation of monocytes into functional DCs might improve the survival of PDAC patients.
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